Pleuro-pulmonary manifestations of systemic/extrapulmonary disorders

1
Pleuro-pulmonary manifestationsofsystemic/extrap
ulmonary disorders

• 
  
• 
  (part I)
• 
  By
• Dr.
  Rehab Maher
  lecturer of chest diseases
  faculty of medicine-Ain
  shams university
• 
  (rehabmahermuhamed_at_hotmail.com)

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Objectives

• systemic /extrapulmonary diseases with
  pleuro-pulmonary manifestations
• Definition
• classification
• - inherited
• - acquired
• - others
• 
  
• pleuro-pulmonary manifestations of
  systemic diseases
• - pulmonary pneumonitis , fibrosis,
• - pleural pleurisy, pleural effusion ,
  pleural thickening , pnthx

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Relevant investigations

• 1. non-invasive
• laboratory values biological blood parameters
  for diagnosis of
• systemic
  diseases
• radiology chest x-ray, ultrasound, CT, MR
• nuclear techniques,
• lung function tests
• 2. invasive
• bronchoscopy including broncho -alveolar lavage
  , TBLB,
• thoracocentesis,
• pleural biopsy
• Related complications
• 
  
  
• Relevant therapeutic measures (pharmacology of
  drugs used)
• 
  

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Respiratory manifestations of immunodeficiency
disorders

• Classification
• 1) congenital immunodeficiency
• immunoglobulin deficiency syndromes and
  defects in cell-
• mediated immunity
• 2) acquired immunodeficiency
• HIV/AIDS,
• organ transplantation,
• lymphoma,
• cytotoxic chemotherapy,
• immunosuppressive drugs,
• malnutrition
  
  
• 
  
  

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• Respiratory clinical features includes
• -infections
• -Non-infectious respiratory manifestations
• pulmonary oedema,
• pulmonary haemorrhage and infarction,
• malignancy,
• autoimmune vasculitis,
• radiation and drug-induced pneumonitis
• Relevant investigations
• 1.Non invasive
• chest X-ray, CT, ultrasound, pulmonary function
  testing, microbiology of spontaneous and induced
  sputum
• 2. invasive
• bronchoscopy, broncho-alveolar lavage, TBLB,
  thoracocentesis
• Prevention and treatment

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Pleuro -pulmonary manifestations of systemic
diseases

• Definition
• These are diseases primarily of other
  organs in which
• lung manifestations may occur and , in some
  cases may be an important presenting feature

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• 
  Classification
• Inherited disorders acquired
  others
• -cystic fibrosis
  -rheumatoid disease
  -rheumatic fever
• -a1 antitrypsin def. -SLE
  
  -ulcerative colitis
• -sickle cell dis.
  -systemic sclerosis
  -Chron disease
• -neurofibromatosis -Sjogren
  syndrome -Whipple
  disease
• -tuberous sclerosis
  -ankylosing spondylitis
  -coeliac disease
• -Ehler Danlos
  -dermatomyositis
  -acute pancreatitis
• -Marfan synd.
  -polyarteritis
  -Waldenstrom macrogl
• -cutis laxa synd. -Behcet
  synd.
  -neuromascular disease
• -Hermansky-Pudlak synd. -relapsing
  polychondritis

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I.Inherited disorders

• Cystic fibrosis
  (mucoviscidosis)
• -AR inheritance (occurance of carrier state Rr)
• - defect in the gene on chromosome 7 encoding for
  CFTR protein
• abnormal Na and Cl ion
  transport across
• the epithelial membrane
• - lungs, pancreas then GIT bear the predominant
  burden of clinical expression 80
  reccurent resp. infectionpanc.insuff.
• 15
  reccurent resp. infectionN.panc.fun.
• 
  5GIT symptoms only
• - All sweat glands are affected
• - Clinical picture starts at birth
  with meconium ileus
• 
  early childhood reccurent resp. infection
• 
  later in life

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Pathophysiology of airways epithelium and mucus
glands in cystic fibrosis

• - Normally,Na is transported with water via
  epithelial Na channels
• In the apical membrane and then transported out
  by Na-K ATP-ase
• And water follows by osmosis limits
  vol. of pericilliary fluid layer
• - In order to rehydrate airway surface,
  relatively low intracellular Na
• enters from Na-K-Cl cotransporter on the serosal
  surface and then
• Cl exits from CFTR,ORCC on the mucosal surface
  followed by water
• 
  rehydrates the mucosal surface
• In cystic fibrosis CFTR defect leads o impaired
  outward movement of Cl with relative dehydration
  of the pericilliary movement
• inhibits mucociliary clearance
  ? adherence/colonization
• 
  reccurent respiratory infections

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Clinical picture

• - At birth abdominal distension
  failure to pass meconium
• bile stained
  vomiting
• -Prolonged neonatal jaundice
• - failure to thrive (obvious by 6 ms . In
  75-80)
• - Reccurent respiratory tract infection
• - variable onset
• - usually begins with
  persistent cough
• -wheezing is common (50)
• - Pseudomonas aeurogenosa is
  the major pathogen
• - Nasal polyps and chronic sinusitis

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Diagnostic tools

• 1.Sweat chloride test
• -gold standard
• - ?50 mmol for Na, Cl
  normal
• 50-70 mmol
  equivocal
• ?70 mmol
  diagnostic
• - single positive test confirmed
  with genotyping
• - false positive in dry skin ,
  eczema
• 2. Nasal potential difference
• 3. Tests for pancreatic function
• -total fecal fat in stools is
  gold standard
• 4. Genetic tests
• -PCR allows genotyping on blood
  spot or mouth rinse
• 5.Microbiological sputum examination

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• 6.Radilogical
• abdomen rt. lower abdominal
  opacification distended
• small intestinal
  loops in the lt. hypochondrium

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Respiratory complications and management

• - Main cause of morbidity and mortality
• a. progressive pulmonary pathology
• 
  infection
• bronchitis/bronchiolitis
  ulcerative bronchitis
• bronchiectasis
  br. wall dilatation
• - affects more proximal airways
• - most marked in upper zones
• - end stage cysts PHTN, cor
  pulmonale ,RF

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• CXR variable with disease progression

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b.Atelectasis and colapse

• - Mainly due to obstruction by secretion
• ttt of a ,b proper abios
  phsysiotherapy /- FOB suction
• c. Haemoptysis
• - commonly small in amounts due to infective
  exacerbation
• - sometimes massive due to bleeding from
  bronchial artery
• - ttt symptomatic
• repeated/persistent
  bronchial artery embolization
• 
  under radiographic guidance
• d.Pneumothorax
• - spontaneous
• - more in males (20)
• - may be associated with poor prognosis
  (assocaited cystic changes)

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• - ttt small conservative oxygen
  therapy
• large ICT drainage
• persistent surgery (limited
  abrasion pleurodesis)
• N.B. pleurectomy is contraindicated due to
  possible future lung
• transplantation risk of bleeding
• e. Respiratory failure
• - begins with type I and progresses to type
  II
• - ttt proper oxygen therapy

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Treatment tips in cystic fibrosis

• -ttt of colonization of Pseuomonas aeurogenosa
• intermittent oral ciprofloxacin
• Or nebulized abios
  (pipracillin/tazobactam, amikacin)
• Ttt of Aspergillus fumigatus
• itraconazole corticosteroids
• - vaccination
• - poly valent vaccine
• - Ps vaccine
• - Influenza vaccine is standard in
  pts. With CF
• - Lung transplantation is key curative surgery

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Tuberous sclerosis

• - AD inheritance
• - two mutations identified
• 1.on chromosome 9q encoding for hamartin
  protein
• 2. on chromosome 16 p encoding for GTPase-
  activating protein
• abnormal
  hamartomatous malformations
• Clinical picture includes
• - skin lesions ( depigmentations up
  to warty nodules)
• - CNS lesions ( nodules causing
  epilepsy, mental retardation)
• - hamartomas of kidneys , heart ,
  bones
• - pulmonary lesions in the form of multiple
  hamartomas reccurent
• 
  pnthx.
• N.B. Carney s triad pulmonary hamartomas
  gastric leiomyosarcoma
• 
  paraganglionoma

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Marfans syndrome

• - AD inheritance
• - mutation identified on chromosome 15 encoding
  for fibrillin protein
• neccesary in elastin containing tissues
  
• reduces tensile strength of
  CT in the suspensory ligament
• of the lens and major blood
  vessels
• - ch.ch. By - excessive height
  disproportionate long limbs , digits
• - dislocation of the lens
• - CVS ( AR , dissecting
  aortic aneurysm, MVP)
• - joint dislocation (lax
  ligaments)
• - Death usually occurs in middle age due to CVS
  affection
• - pulmonary involvement includes
• -pnthx
• - upper lobe
  bullae /- fibrosis
• -
  aspergillomas may complicate bullae
  

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Sickle cell disease

• - Sickle cell disease (homozygotes) inherit Hb S
  from both parents
• - Sickle cell trait (heterozygotes) have Hb S
  Hb A and only show
• evidence of sickling when stressed by hypoxia
• - Hb S has valine instead of glutamic acid in
  the ß chain due
• to mutation in chromosome 11
• - Sickle cell disease is ch.ch. By sickling
  crisis
• - vascular occlusion
  by deformed RBCs
• - bone marrow aplasia
  
• - pulmonary manifestations
• - acute chest syndrome fever
  pain tachypnea inspiratory crackles
  consolidative signs in CXR falling Hb
• - pulmonary infarction
• - repeated episodes PHTN
  
• - ttt narcotic analgesics oxygen IV fluids
  abios
• if no improvement exchange
  transfusion

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Hermansky Pudlak syndrome

• -AR inheritance
• - defect on chromosome 10q encoding for
  transmembrane peptide
• -albinism platelet aggregation defect BM
  inclusions
• -pt. c/o bruising , menorrhagia in females ,
  bleeding
• - lung involvement inludes
• interstitial fibrosis
• chronic alveolar haemorrhage
  haemosiderosis

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II. acquired disorders

• Respiratory manifestations of connective tissue
  diseases
• a. Rheumatoid disease
• -Pleural effusion/fibrosis
• -pulmonary nodules and diffuse fibrosis
• -Caplan 's syndrome
• - Bronchopleural fistula
• -bronchiolitis obliterans
• -pulmonary hypertension
• -bronchiectasis
• -bronchocentric granuloma
• -eosinophilic pneumonia
• -recurrent infections
• -amyloidosis
• -shrunken lung
• -cricoarytenoid obstruction

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• b.Systemic lupus erythematosis
• -Pleurisy / pleural effusion
• -Pulmonary hypertension/embolism
• -pulmonary haemorrhage
• -acute pneumonitis (lupus pneumonitis )
• -interstitial fibrosis
• -lymphocytic interstitial pneumonitis
• -segmental atelectasis
• -diaphragmatic dysfunction
• -infections
• -amyloidosis
• c.systemic sclerosis
• -pulmonary fibrosis
• -pulmonary hypertension
• -aspiration pneumonia
• -relapsing pneumonitis

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• d.Syjogren's syndrome
• -xerotrachea
• -pulmonary fibrosis
• -lymphocytic interstitial pneumonitis
• -pulmonary lymphoma
• e.Ankylosing spondylitis
• -restricted chest movement
• -upper lobe fibrosis
• f.dermatomyositis/polymyositis
• -interstitial fibrosis
• g.Polyarteritis nodosa/giant cell arteritis
• -pulmonary arteritis/infarction

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• h.Mixed connective tissue disease
• -pleurisy/pleural effusion
• -interstitial fibrosis
• -pulmonary arteritis
• i.Behcet's disease
• -pulmonary arteritis
• - Pulmonary infarction
• j.Relapsing polychondritis
• -tracheal stenosis
• -recurrent infetions

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Rheumatoid disease

• - an autoimmune disease
• - chronic inflammation of the joints and other
  areas of the body
• - multiple joints are usually, but not always,
  affected symmetrically
• - can cause permanent joint destruction and
  deformity
• - rheumatoid factor antibody can be found in
  80 of pts.
• - characterized by periods of disease flares and
  remissions.
• - other signs include firm subcutaneous nodules
  (rheumatoid nodules)
• - first line drugs are NSAIDs , corticosteroids
  

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• 1.Pleural disease
• Pleural effusion/ thickening/fibrosis
• -more in males
• -middle age
• -usually effusion follows joint
  involvement
• -commonly small and asymptomatic
• -Tends to reccur after aspiration
• -Thoracocentesis exudative fluid
  with
• high protein content ,
• high pl. fluid/serum
  ratio of neurone-specific enolase
• high chlesterol
  content
• low glucose
  content(diagnostic)
• /-high titre of
  rheumatoid factor in pl. fluid
• cellsPMNLs,epithelioid
  cells leucocytes with dense granules.
• - pl. biopsy palisaded
  histiocytes

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• - ttt
• -small asymptomatic
  effusion no ttt
• -larger effusion
  aspiration
• 
  reccurent pleurodesis
• post effusion
  pl.fibrosis
• pleurectomy
• N.B. -role of steroids in rheumatoid pleural
  effusion is controversial
• a trial is justified in
  reccurent cases before pleurodesis

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2.Pulmonary fibrosis

• -commonest pulmonary complication of
  rheumatoid disease
• -in 30-40 of patients
• -slowly progressive
• -diffuse
• -maximal in lower zones
• -finger clubbing occurs in 50 of patients
• -bilateral fixed basal crackles are
  charecteristic
• -radilogical diffuse nodular infiltrates
  predominantly
• in lower zones up to
  honeycombing pattern
• -lung function restrictive pattern
• -Dlco may show diffusion defect
• -cannot be differentiated from the
  cryptogenic pul . Fibrosis
• -ttt stationary course requires no ttt
  just follow up every 6 ms
• while progressive course
  steroids1mg/kg/d max.60 mg
• alone or with azathioprine,cyclophasphami
  de,penicillamine

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• 3.Pulmonary nodules
• -least common lung manifestation of
  the disease
• -single or multiple
• -1-3 ms in size
• -tend to be subpleural
• -typically cavitate leaving a thin
  line cavity
• -does not correlate to disease
  severity
• -associated with the presence of
  subcutaneous nodules
• as well as high titre of
  rheumatoid factor
• -histologially central caseation
  surrounded by palisaded
• histiocytes and peripheral zone of
  ch. Inflammatory cells
• -when occurs in lungs of coal
  workers Caplan's syndrome
• - may be complicated by BPF
• -No treatment (excluding
  malignancy)
  

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• multiple rheumatoid
  nodules

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4.Bronchiolitis obliterans

• -wide spread fibrous obliteration of the
  bronchioles
• -on auscultation diffuse inspiratory
  crackles
• -lung function severe airflow obstruction
• -Dlco reduced
• -lung volumes increased residual volume and
  total lung capacity
• -fate progressive form ends in death with
  respiratory failure within
• 2-3 yrs., while in milder forms
  survival may reach 10 yrs. after
• onset of symptoms
• -corticosteroids are ineffective in
  preventing the progression

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Systemic lupus erythematosus(SLE)

• -Aetiology unknown but may follow drug
  intake(hydralazine,phenytoin
• procainamide ,
  chlorpromazine , penicillamine)
  
• -systemic features include-facial rashes
• 
  -discoid skin lesions
• 
  -photosensitivity
• 
  -hair loss
• 
  -arthropathy
• 
  -renal(interstitial nephritis)
• 
  -CNS lesions
• -diagnosis clinical features positive ANA.
  anti double stranded DNA
• 
  antibody lupus cells in blood

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1.Pleurisy and pleural effusion

• -the commenest pleuropulmonary complication in
  those patients
• - may be unilateral or bilateral
• -may reccur
• -pleurisy presents with pleuritic chest pain
  friction rub normal CXR
• ttt NSAIDs
• -exudative fluid- normal glucose content
• -high count of
  mononuclear cells
• -low levels of
  C3,C4, lupus cells , ANA
• -pl. biopsy non specific inflammation
• -Spontaneous resolution is the norm
• -ttt small no ttt
• large apiration /-
  steroids in severe /persistent cases
• N.B. make sure to exclude PE as a cause of pl.
  effusion

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2.Lupus pneumonitis

• - occurs in about 12 of patients ,often severe
  and may be lifethreatening
• - clinically, patient c/o fever , breathlessness
  . cough /- haemoptysis
• crackles all over the chest /-
  cyanosis(hypoxemia)
• - CXR -pneumonic infiltrates mostly bilateral
  and basal
• - may coalasce and form patches
• - /- pleural effusion
• - occasionally. Normal CXR
• - bacteriology is negative
• -ttt high dose of prednisone (60 mg /d) and if
  there is renal involvement
• cyclophosphamide is added
• -The dose is titrated according to clinical
  response (monitored by
• Dlco ) stopping the cyclophosphamide first
  then reducing steroids
• to a low maintenance level

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3. Acute Pulmonary haemorrhage

• - may be fatal , mortality rate is 50
• - Clinically malaise , cough , dyspnea
  cyanosis and haemoptysis
• - CXR bilateral extensive consolidation
• - fall in haemoglobin ( diagnostic clue)
• - D.D. Goodpasture' s syndome ( antiglomerular
  basement membrane
• antibody is positive)
• -ttt oxygenation blood transfusion high dose
  corticosteroids
• cyclophosphamide
• N.B. uraemia,thrombocytopenia are other causes
  of pulmonary
• haemorrhage in SLE
  

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4.Pulmonary embolism/infarction

• - is a particular risk in SLE patients with
  positive lupus anticoagulant
• - lupus anticoagulant (antiphospholipid
  antibody)
• with two paradoxical effects
• 1. interferes with
  transforming prothrombin to thrombin
• 
  prolonged ptt
• 2.inhibits release of
  arachidonic acid metabolites
• loss of
  their inhibitory effects
• ?
  platelet aggregation/thromboses
• - Associated with CNS involvement , reccurent
  abortions in females

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5. Vanishing lung syndrome

• - Patients presents with progressive exertional
  dyspnea
• - no abnormal clinical signs
• - lung function shows restrictive pattern
• - limited diaphragmatic excursion on screening
• - transdiaphragmatic pressure is reduced
• - mostly due to respiratory myositis
• - good response to corticosteroids

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Systemic sclerosis

• - A multisystem disease ch.h. by
• -
  fibrosis of the epidermis and dermis,
• -
  fibrosis of skeletal muscles
• -
  fibrosis of internal organs(renal,heart
  lungs,GIT)
• -
  Raynaud's phenomenon
• - Most cases, aetilogy is obscure
• - More in females (31) with peak incidence in 20
  60 yrs.
• - prognosis depend on organs involved(5- year
  survival is 70 )
• - renal /cardiac involvement is the main cause
  of death
• - scleroderma is a benign variant with only skin
  involvement
• - CREST is another variant with - calcinosis
  of the finger tips
• 
  - Raynaud's phenomenon
• 
  - esophageal dysfunction
• 
  - sclerodactyly
• 
  - telangiectasis (skin)
• - Main pathological features occur in small
  vessels
• - circulating anti nuclear antibodies(anti-Scl 70
  antibody) are positive in 90
  

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1.Pulmonary fibrosis

• - occurs in most patients
• - less progressive than idiopathic type
• - presents with progressive exertional dyspnea
• bilateral basal
  inspiratory crackles
• CXR showing bilateral
  mainly basal fine irregular lines
• lung function showing
  restrictive pattern with ? Dlco
• - dyspnea , out of proportional to radiology/-
  lung function
• 
  suspect additional vascular affection
• - cor pulmonale is rare

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2.Pulmonary hypertension

• - progressive complication particularly in CREST
  syndrome
• - bad prognosis (death within 3 yrs.)
• - Wide spread obliterative changes in pul.
  arteries and arterioles
• - dyspnea is rapidly progressive
• - clinical signs of pulmonary HTN are - rt.
  Ventricular heave
• 
  - large jugular a waves
• 
  - accentuated S2
• - cor pulmonale usually develops
• - CXR may be normal, avascular, dilated
  pulmonary arteries
• - ECG shows signs of rt. Ventricular hypertrophy
• - lung function shows severly reduced Dlco
• - vasodilators (hydralazine , ACE inhibitors ,
  Ca channel blockers )
• may be tried but are generally unsuccessful

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Sjogrens syndrome

• -Primary Sjogrens is a syndrome ch.ch. By dry
  eyes , mouth and other mucus membranes ,
  lymphocytic infiltration of salivary and other
  mucus glands
• - mostly associated with Rh. Arthritis , SLE ,
  Raynaud s disease , scleroderma
• - Pulmonary involvement includes
• -
  xerotrachea persistent dry cough
• - airway
  narrowing
• -
  interstitial lung disease (fibrosis or diffuse
  infiltrates)
• - risk of
  malignant lymphoma , reticulum cell carcinoma
• -
  respiratory infection and pneumonia
• - ttt - no curative ttt for the syndrome
• - clinically progressive fibrosis
  high dose corticosteroids
• - lymphoma
  appropriate chemotherapy

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Ankylosing spondylitis

• - slowly progressive inflammation of spinal
  joints leading to ankylosis
• - predominantly , in young adult males
• - strong genetic association with HLA-B 27
  antigen in 90 of cases
• - spine involvement ranges from sacroiliac joint
  only up to rigid
• bamboo spine
• - Presents with low backache often referred to
  the back of both
• legs with morning stiffness
• - no ttt is required

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• - pulmonary involvement
• - Usually in a pt. with long history of the
  disease
• - two conditions are recognized
• - restrictive pattern secondary to
  thoracic affection
• usually insufficient
  to cause dyspnea because it is
• compensated by
  diahragmatic function
• - upper lobe fibrosis
• rarely
  progressive
• diagnostic puzzle
  if association is not known
• may be
  complicated with bronchiectasis
• may be seated
  with aspergillomas
• 
  
• 
  haemoptysis

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Behcet s syndrome

• - Ch. Ch. By - reccurent oral and genital
  ulceration,
• - iritis
• - thrombophlebitis and
  arteritic lesions
• - pulmonary involvement includes
• -pulmonary arteritis with
  multiple reccurent infarcts
• 
  haemoptysis
• - pulmonary artery aneurysm
• - ttt - high dose prednisolone and
  cyclophosphamide
• N.B. Hughes Stovin syndrome is a variant of the
  disease reccurent
• thrombophlebitis pulmonary artery
  vasculitis aneurysm

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Rheumatic fever

• - Acute pulmonary effects of heart failure
• - Rheumatic pneumonia
• pulmonary infiltrative
  condition
• presents with cough , dyspnea ,
  pleurisy /-haemoptysis
• CXR shows patchy mottling
• organization with fibrosis may
  occur
• corticosteroids are recommended

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Bibliography

• Plz refer to
• (pulmonary manifestations of systemic
  disease)
• in
• Crofton And Douglas's Respiratory Diseases
  fifth edition

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